Cortical auditory evoked potentials in children who stutter

Publication date: Available online 3 April 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Naema Ismail, Yossra Sallam, Reda Behery, Ameera Al Boghdady
IntroductionIt has been hypothesized that impaired auditory processing influence the occurrence of stuttering. Also, it is suggested that speech perception in children who stutter differed from normal. Auditory processing should be investigated in children who stutter shortly after the onset of stuttering in order to evaluate the extent to which impaired auditory processing contributes to the development of stuttering. CAEPs provide the necessary temporal and spatial resolution to detect differences in auditory processing and the neural activity that is related or time-locked to the auditory stimulus. The primary goal of the present study was to determine the difference in latency and amplitude of P1-N2 complex between children who stutter and non-stuttering children in response to speech stimuli.Material & MethodsThis case-control study was performed over 60 children, 30 were non-stuttering children (control group) and 30 were children who stutter (study group) ranging in severity from Bloodstien I to Bloodstien IV in the age range of 8-18 years.ResultsCAEPs of children who stutter with stuttering severity Bloodstien IV showed significant prolonged latencies and reduced amplitudes when blocks and IPDs were the most predominant core behaviors. P1 and N1 were prolonged in concomitant behaviors.ConclusionIt could be speculated that speech processing was affected in children who stutter with stuttering severity Bloodstien IV at the level of early perceptual auditory cortex.



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The applications of POEM for special patient cohorts: a review

Abstract

Peroral endoscopic myotomy (POEM) is a relatively mini-invasive technique which can perform endoscopic myotomy by establishing a submucosal tunnel, and it has been firstly applied in animals since 2007.¹

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Comparison cisplatin with cisplatin plus 5FU in head and neck cancer patients received postoperative chemoradiotherapy

Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Chien-Chih Chen, Jin-Ching Lin, Kuan-Wen Chen
PurposeTo compare the treatment outcomes and toxicity of both cisplatin and cisplatin plus 5FU chemotherapy in head and neck cancer patients who have received surgery, in addition to postoperative chemoradiotherapy.Materials and methodsFrom May 1991 to December 2012, a total of 113 head and neck cancer patients who received surgery, along with postoperative chemoradiotherapy were analyzed. The primary sites were oral cavity (86), oropharynx (17), hypopharynx (4), and larynx (6). Thirty-nine patients received cisplatin (P), while 74 patients received cisplatin plus 5FU (PF). The endpoints were overall survival (OS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS).ResultsThe median follow up time was 43months, with a range of 4–222months. The 3-year rates of OS, LFFS, and DMFS were 62.1%, 71.3%, and 82.4%, respectively. The 3-year OS for P and PF were 71.3% and 57.5% (p=0.27).A multivariate analysis revealed that various chemotherapy regimens displayed no statistical difference for OS (Hazard Ratio [HR]=1.81; 95% Confidence Interval [CI]=0.963–3.408; p=0.065), LFFS (HR=0.98; 95% CI=0.458–2.127; p=0.973), and DMFS (HR=1.25; 95% CI=0.463–3.398; p=0.656).Grade 3 and 4 mucositis for P and PF group were 61.5% and 64.9%. A greater than grade 3 dermatitis for P and PF group were 7.7% and 14.9%.ConclusionPostoperative chemoradiotherapy with cisplatin alone appeared to have higher 3-year OS and lower severe mucositis and dermatitis than cisplatin plus 5FU.



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Establishment and characterization of an oral tongue squamous cell carcinoma cell line from a never-smoking patient

Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Steven J. Wang, Saurabh Asthana, Annemieke van Zante, Chase M. Heaton, Janyaporn Phuchareon, Leighton Stein, Saito Higuchi, Tomoya Kishimoto, Charles Y. Chiu, Adam B. Olshen, Frank McCormick, Osamu Tetsu
ObjectiveThe rising incidence of oral tongue squamous cell carcinoma (OTSCC) in patients who have never smoked and the paucity of knowledge of its biological behavior prompted us to develop a new cell line originating from a never-smoker.Materials and methodsFresh tumor tissue of keratinizing OTSCC was collected from a 44-year-old woman who had never smoked. Serum-free media with a low calcium concentration were used in cell culture, and a multifaceted approach was taken to verify and characterize the cell line, designated UCSF-OT-1109.ResultsUCSF-OT-1109 was authenticated by STR DNA fingerprint analysis, presence of an epithelial marker EpCAM, absence of human papilloma virus (HPV) DNA, and SCC-specific microscopic appearance. Sphere-forming assays supported its tumorigenic potential. Spectral karyotype (SKY) analysis revealed numerical and structural chromosomal abnormalities. Whole-exome sequencing (WES) identified 46 non-synonymous and 13 synonymous somatic single-nucleotide polymorphisms (SNPs) and one frameshift deletion in the coding regions. Specifically, mutations of CDKN2A, TP53, SPTBN5, NOTCH2, and FAM136A were found in the databases. Copy number aberration (CNA) analysis revealed that the cell line loses chromosome 3p and 9p, but lacks amplification of 3q and 11q (as does HPV-negative, smoking-unrelated OTSCC). It also exhibits four distinctive focal amplifications in chromosome 19p, containing 131 genes without SNPs. Particularly, 52 genes showed >3- to 4-fold amplification and could be potential oncogenic drivers.ConclusionWe have successfully established a novel OTSCC cell line from a never-smoking patient. UCSF-OT-1109 is potentially a robust experimental model of OTSCC in never-smokers.



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Comparison cisplatin with cisplatin plus 5FU in head and neck cancer patients received postoperative chemoradiotherapy

Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Chien-Chih Chen, Jin-Ching Lin, Kuan-Wen Chen
PurposeTo compare the treatment outcomes and toxicity of both cisplatin and cisplatin plus 5FU chemotherapy in head and neck cancer patients who have received surgery, in addition to postoperative chemoradiotherapy.Materials and methodsFrom May 1991 to December 2012, a total of 113 head and neck cancer patients who received surgery, along with postoperative chemoradiotherapy were analyzed. The primary sites were oral cavity (86), oropharynx (17), hypopharynx (4), and larynx (6). Thirty-nine patients received cisplatin (P), while 74 patients received cisplatin plus 5FU (PF). The endpoints were overall survival (OS), local failure-free survival (LFFS), and distant metastasis-free survival (DMFS).ResultsThe median follow up time was 43months, with a range of 4–222months. The 3-year rates of OS, LFFS, and DMFS were 62.1%, 71.3%, and 82.4%, respectively. The 3-year OS for P and PF were 71.3% and 57.5% (p=0.27).A multivariate analysis revealed that various chemotherapy regimens displayed no statistical difference for OS (Hazard Ratio [HR]=1.81; 95% Confidence Interval [CI]=0.963–3.408; p=0.065), LFFS (HR=0.98; 95% CI=0.458–2.127; p=0.973), and DMFS (HR=1.25; 95% CI=0.463–3.398; p=0.656).Grade 3 and 4 mucositis for P and PF group were 61.5% and 64.9%. A greater than grade 3 dermatitis for P and PF group were 7.7% and 14.9%.ConclusionPostoperative chemoradiotherapy with cisplatin alone appeared to have higher 3-year OS and lower severe mucositis and dermatitis than cisplatin plus 5FU.



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Establishment and characterization of an oral tongue squamous cell carcinoma cell line from a never-smoking patient

Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Steven J. Wang, Saurabh Asthana, Annemieke van Zante, Chase M. Heaton, Janyaporn Phuchareon, Leighton Stein, Saito Higuchi, Tomoya Kishimoto, Charles Y. Chiu, Adam B. Olshen, Frank McCormick, Osamu Tetsu
ObjectiveThe rising incidence of oral tongue squamous cell carcinoma (OTSCC) in patients who have never smoked and the paucity of knowledge of its biological behavior prompted us to develop a new cell line originating from a never-smoker.Materials and methodsFresh tumor tissue of keratinizing OTSCC was collected from a 44-year-old woman who had never smoked. Serum-free media with a low calcium concentration were used in cell culture, and a multifaceted approach was taken to verify and characterize the cell line, designated UCSF-OT-1109.ResultsUCSF-OT-1109 was authenticated by STR DNA fingerprint analysis, presence of an epithelial marker EpCAM, absence of human papilloma virus (HPV) DNA, and SCC-specific microscopic appearance. Sphere-forming assays supported its tumorigenic potential. Spectral karyotype (SKY) analysis revealed numerical and structural chromosomal abnormalities. Whole-exome sequencing (WES) identified 46 non-synonymous and 13 synonymous somatic single-nucleotide polymorphisms (SNPs) and one frameshift deletion in the coding regions. Specifically, mutations of CDKN2A, TP53, SPTBN5, NOTCH2, and FAM136A were found in the databases. Copy number aberration (CNA) analysis revealed that the cell line loses chromosome 3p and 9p, but lacks amplification of 3q and 11q (as does HPV-negative, smoking-unrelated OTSCC). It also exhibits four distinctive focal amplifications in chromosome 19p, containing 131 genes without SNPs. Particularly, 52 genes showed >3- to 4-fold amplification and could be potential oncogenic drivers.ConclusionWe have successfully established a novel OTSCC cell line from a never-smoking patient. UCSF-OT-1109 is potentially a robust experimental model of OTSCC in never-smokers.



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Tryptase potentiates enteric nerve activation by histamine and serotonin: Relevance for the effects of mucosal biopsy supernatants from irritable bowel syndrome patients

Abstract

Background

We previously showed that mucosal biopsy supernatants from irritable bowel syndrome patients activated neurons despite low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We studied the potentiating responses between these mediators on excitability of enteric neurons.

Methods

Calcium-imaging was performed using the calcium-sensitive dye Fluo-4 AM in human submucous plexus preparations from 45 individuals. Histamine, serotonin, and tryptase were applied alone and in combinations to evaluate nerve activation which was assessed by analyzing increase in intracellular Ca²⁺ ([Ca²⁺]_i), the proportion of responding neurons and the product of both defined as Ca-neuroindex (NI). Protease activated receptor (PAR) 2 activating peptide, PAR2 antagonist and the serine protease-inhibitor FUT-175 were used to particularly investigate the role of proteases.

Key Results

Histamine or serotonin (1 μmol/L each) evoked only few small responses (median NI [25%/75%]: 0 [0/148]; 85 [0/705] respectively). Their combined application evoked statistically similar responses (216 [21/651]). Addition of the PAR2 activator tryptase induced a significantly higher Ca-NI (1401 [867/4075]) compared to individual application of tryptase or to coapplied histamine and serotonin. This synergistic potentiation was neither mimicked by PAR2 activating peptide nor reversed by the PAR2 antagonist GB83, but abolished by FUT-175.

Conclusions & Inferences

We observed synergistic potentiation between histamine, serotonin, and tryptase in enteric neurons, which is mediated by proteolytic activity rather than PAR2 activation. This explained neuronal activation by a cocktail of these mediators despite their low concentrations and despite a relatively small PAR2-mediated response in human submucous neurons.

Biopsy supernatants of irritable bowel syndrome patients activate enteric neurons despite the low concentrations of tryptase, histamine, and serotonin which individually would not cause spike discharge. We found that tryptase synergistically potentiated the response to individual and combined application of histamine and serotonin. This potentiation was mediated by proteolytic activity of tryptase rather than protease activated receptor 2 activation. Our findings identified synergism between neuroactive substances as a plausible explanation for their pronounced effects as a cocktail.

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